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Biomedical subjects

M C Neville

Publications and source records attributed to M C Neville.

At least 91 records · Page 5Linked to original sources

Spin-lattice relaxation times for 13C in isotope-enriched glycine accumulated in frog muscle.

Spin-lattice relaxation times (T1's) of 13C-enriched glycine accumulated in frog muscles were determined at 1 degrees C by the inversion-recovery (180 degrees -tau-90 degree pulse sequence) method and compared with the values obtained in free solution. The value of T1 for the alpha-13C nucleus of glycine in the tissue was 50% of that obtained in free solution. The observed value for T1 in the tissue was not concentration-dependent, and no difference in chemical shift was observed between tissue and free solution. Quantification of the area under the glycine peak suggested that the observed signal represents at least 80% of the intracellular glycine. An average nuclear Overhauser enhancement of 2.83 for intracellular glycine indicates that the relaxation mechanism within the cell is predominantly dipolar, as in free solution. The value of T1 for the 13C' nucleus of glycine in the tissue was 67% of that in a solution of similar concentration. A quantitative analysis of the findings suggests that the observed difference in the value of T1 between tissue and free solution results from a difference in viscosity. The data provide no evidence either for special organization of intracellular water or for glycine binding. It is proposed that intracellular diffusion coefficients may be determined from measurements of 13C T1's of 13C-enriched intracellular solutes.

Animals↗

Antiprotozoal thiazoles. 2. 2-(5-Nitro-2-furyl-, thiazolyl-, and 1-methylimidazolyl-)thiazoles.

Ten 2-substituted 4-thiazolecarboxaldehyde hydrazones bearing 5-nitro-2-furyl, 5-nitro-2-thiazolyl, and 1-methyl-5-nitro-2-imidazolyl functions have been prepared and screened for activity against Trypanosoma cruzi infections in mice. The results permitted the ranking of these substituents in decreasing order of activity: 1-methyl-5-nitro-2-imidazolyl greater than 5-nitro-2-furyl greater than 5-nitro-2-thiazolyl, the last being inactive. Some structural features of the side chain necessary for optimum activity are discussed. The most active compound, 4-[[[2-(1-methyl-5-nitro-2-imidazolyl)-4-thiazolyl]methylene]amino]thiomorpholine 1,1-dioxide, compared favorably with the standard Nifurtimox against three recent clinical isolates of T. cruzi, including one with a high myocardial tissue infiltration.

Animals↗

Amino acid accumulation in frog muscle. II. Are cycloleucine fluxes consistent with an adsorption model for concentrative uptake of amino acid?

Cycloleucine accumulation by frog muscle was studied at 0 degrees C and 25 degrees C. At external concentrations less than 5 mM the distribution ratio of cycloleucine is higher at 0 degrees C. At concentrations greater than 5 mM the converse is true due to apparent exclusion of cycloleucine from a larger portion of the cell water at 0 degrees C than at 25 degrees C. The steady state data are consistent with an adsorption model for amino acid accumulation. Flux studies provide a means to rule out this model if all the possible rate-limiting steps in the movement of amino acid into and out of the cell are considered. These steps include intra-cytoplasmic diffusion, desorption from cytoplasmic or membrane sites and passage through the cell membrane. The assumption is made that the rate-limiting step for influx and efflux is the same, allowing the use of either influx or efflux data to examine the model. Diffusion-limited flux is ruled out on the basis of "influx profile analysis" of the time course of cycloleucine entry at both 0 degrees C and 25 degrees C. At least 95% of all intracellular cycloleucine leaves frog muscle cells with a single exponential time course at both 0 degrees C and 25 degrees C. The rate constant of efflux does not vary with cellular concentration. These findings are shown to be incompatible with desorption-limited efflux. They are compatible with membrane-limited efflux only if (i) adsorption sites are located on membranes with direct access to the extracellular space and (ii) the rate constant for desorption is equal to the rate constant of membrane-limited efflux of free amino acid. It is considered unlikely that such a coincidence would occur at both 0 degrees C and 25 degrees C. Therefore, an adsorption model for cycloleucine accumulation in frog muscle appears to be untenable.

Amino Acids↗

An electrogenic component of the potential difference in the rabbit lens.

The normal resting potential of the rabbit lens, -70mV, is altered to -59mV by ouabain concentrations up to 5-1- minus 6M, and to -52mV at 4 degrees C. Ouabain acts only at the anterior lens surface. The temperature effect id completely reversible. The Hodgkin-Katz-Goldman equation can be used with the measured lens potentials and Na+ and K+ levels in the lens and bathing medium to obtain alpha, the ration of the membrane permeabilities to Na+ and K+. The alpha-values obtained were 0.052 at 4 degrees C and 0.053 in 5-10 minus 6M ouabain. These data suggest that the change in potential due to cold and ouabain is caused by an inhibition of an electrogenic Na+ ump in the anterior lens epithelium.

Animals↗

Nuclear magnetic resonance studies and water "ordering" in the crystalline lens.

Nuclear magnetic resonance studies of the relaxation times of the water in the crystalline lens show that, as in all interfacial systems, these parameters are markedly reduced from their values in pure water, that T(2) is less than T(1), and that both depend on water content. Determination of diffusion coefficients and studies on physiologically inert lenses indicate that reduced relaxation times do not provide direct evidence for ordering of the bulk of the cell water.

Animals↗

Solute concentration gradients in frog muscles at 0 degree C: active transport or adsorption?

In isolated frog muscle that has been incubated for 7 days at 0 degrees C invitro K(+) and Na(+) remain at normal concentrations. Amino acids are accumulated against a concentration gradient at this temperature; for example, glycine accumulates in muscle to a concentration ten times that in the external solution. The amount of cycloleucine accumulated is greater at 0 degrees C than at 25 degrees C. These findings, which are difficult to explain on the basis of metabolically linked active transport, are Consiststent with the view that solute accumulation by cell is the result of adsorption on spesific sites.

Adsorption↗

Lipid composition of prepartum human mammary secretion and postpartum milk.

Changes in lipid composition of mammary secretions of five women were studied at two prepartum periods and compared with composition of colostrum, transitional, and mature human milk. Fat content was approximately 1 g/dl during early (-42.0 days before parturition) and late (-9.5 days) prepartum periods and increased to 3-4 g/dl in colostrum (3.0 days post partum), transitional (7.2 days), and mature milk (56.2 days). Most of the lipid present was triglyceride either pre- (93%) or post- (97%) partum. All fat globule core lipids, with the exception of 1,3-diglycerides, increased from prepartum concentrations to levels usually found in milk. Prepartum secretions contained higher amounts of the membrane components, phospholipid (3.2 g/dl), cholesterol (2.3 g/dl), and cholesteryl ester (1.1 g/dl), which declined postpartum to 0.65, 0.37, and 0.09 g/dl, respectively. Thus, the content of core lipids exhibited an opposite pattern to the content of membrane lipids pre- and postpartum. With regard to synthesis of fatty acids, prepartum secretory mechanisms appeared to be very similar to those occurring postpartum since fatty acid composition of prepartum secretions closely resembled that of postpartum milk.

Breast↗

Diurnal and within-feed variations in lipase activity and triglyceride content of human milk.

This study examined the diurnal and within-feed variations in the two lipases of human milk, bile-salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In addition, all milks were also analyzed for triglyceride content. As compared to BSSL, LPL activity was more variable both among mothers and among different samples from the same mother (largest variation, 0-2.8 U/ml milk). The only significant variation in lipase activity was in LPL activity during a 24-h period (0.96 +/- 0.113, 0.52 +/- 0.21, and 0.57 +/- 0.092 U/ml milk at 0801-1600, 0001-0800, and 1601-2400 h, respectively) (p less than 0.05). Triglyceride content showed no significant diurnal variation but did increase significantly during a single feeding (31 +/- 9.4, 52 +/- 11.7, and 72 +/- 14.8, mumoles triglyceride/ml milk for fore-, mid-, and hind-milks, respectively) (p less than 0.05). There was no correlation between either LPL or BSSL activity and triglyceride content of the milks. Our data indicate that milk obtained for banking or research purposes will contain similar levels of BSSL activity irrespective of diurnal or within-feed timing of milk collections.

Circadian Rhythm↗